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Regulation of 1,25‐dihydroxyvitamin d 3 by calcium in the parathyroidectomized, parathyroid hormone‐replete rat
Author(s) -
Weisinger Jose R.,
Favus Murray J.,
Langman Craig B.,
Bushinsky David A.
Publication year - 1989
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650040618
Subject(s) - endocrinology , egta , medicine , calcium , parathyroid hormone , chemistry , calcitriol , calcium metabolism
Parathyroid hormone (PTH) is a major stimulus for the renal production of 1,25‐dihydroxyvitamin D 3 [1,25‐(OH) 2 D 3 ]. Elevated arterial blood ionized calcium ([Ca 2+ ]) depresses serum 1,25‐(OH) 2 D 3 in nonparathyroidectomized rats even when serum PTH is maintained at high levels by infusion. However, suppression by [Ca 2+ ] of endogenous PTH, causing the fall in 1,25‐(OH) 2 D 3 , cannot be excluded. To determine whether [Ca 2+ ] regulates 1,25‐(OH) 2 D 3 in the absence of a variation in PTH, we parathyroidectomized (PTX) rats (post‐PTX calcium levels <7.0 mg/dl), inserted arterial and venous catheters, and then replaced PTH using an osmotic pump. We varied [Ca 2+ ] by infusing either 75 mM sodium chloride (control), 0.61 μmol/min of EGTA (EGTA), or calcium chloride at 0.61 μmol/min (low calcium) or 1.22 μmol/min (high calcium) for 24 h 5 days after surgery. Blood was then drawn from the rat through the arterial catheter. Compared with the control, [Ca 2+ ] fell with EGTA, remained constant with the low‐calcium infusion, and rose with the high‐calcium infusion. 1,25‐(OH) 2 D 3 was correlated inversely with [Ca 2+ ] in all four groups together (r = −0.635, n = 34, p < 0.001), within the control group alone (r = −0.769, n = 11, p < 0.002), and within the EGTA group alone (r = −0.774, n = 10, p < 0.003). Serum phosphorus, PTH, and arterial blood pH were not different in any group, and none correlated with serum 1,25‐(OH) 2 D 3 . We conclude that 1,25‐(OH) 2 D 3 levels are regulated by [Ca 2+ ] independently of serum PTH, phosphorus, and acid‐base status, all of which support the hypothesis that [Ca 2+ ] is a principal regulator of serum 1,25‐(OH) 2 D 3 in the rat.